T cell antigen receptor (TCR) ligation triggers a cascade of intracellular signaling events that culminate in T cell activation, cytokine gene expression, differentiation, or apoptosis. Many of the enzymes and adapter proteins responsible for signal propagation from the cell surface TCR to the cytoplasm and nucleus have now been identified and molecularly cloned. However, a comprehensive understanding of the regulation and functions of these signaling proteins in T cells remains a major challenge. Our laboratory has approached this problem through the generation of a panel of Jurkat T cell-derived somatic mutants that fail to express several critical elements in the TCR-linked signaling cascade. This review highlights the use of mutant T cell lines for functional characterizations of two of these signaling proteins--the ZAP-70 tyrosine kinase and phospholipase C-gamma1.